Risk of serious skin and subcutaneous tissue disorders for nimesulide among the pediatric population: a jeopardy identified through the analysis of global individual case safety reports.

BACKGROUND: The safety reports arising currently on nimesulide are divulging the jeopardy of skin and subcutaneous tissue disorders (SSTDs). RESEARCH DESIGN AND METHODS: The global individual case safety reports on nimesulide-induced SSTDs available at VigiBase® were analyzed up to 31 March 2023. Disproportionality analyses viz. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were performed to identify the quantitative signals. RESULTS: Out of 33,983,649 de-duplicated cases available in the VigiBase®, 1,664,134 (4.9%) were in pediatrics below 12 years of age. Among these, cases attributed to nimesulide were 251, of which 126 (50.2%) were on SSTDs. Among all the SSTDs reported for nimesulide, the serious reactions like urticaria [PRR = 2.3; lower bound (LB) ROR = 1.7; IC025 = 0.6], Stevens-Johnson syndrome (SJS) [PRR = 28.3; LB ROR = 18.2; IC025 = 3.2], angioedema [PRR = 7.5; LB ROR = 4.5; IC025 = 1.7], and toxic epidermal necrolysis (TEN) [PRR = 27.4; LB ROR = 11.5; IC025 = 1.5] were identified as potential signals. In comparison with non-SSTDs, SSTDs reported for nimesulide were significantly higher among children (2-11 years, 90.5%), from India (38.9%), and by the physician (60.3%). CONCLUSIONS: Identifying the giant quantitate association between nimesulide and serious & life-threatening reactions like SJS and TEN, precautionary measures need to be taken by the regulatory authorities to prevent nimesulide-induced SSTDs among the pediatric population.

Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. RESEARCH DESIGN AND METHODS: A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes. RESULTS: The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC025 = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC025 = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC025 = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; P = 0.03). CONCLUSION: Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.

We conducted this research to identify the risk of pancreatitis and pancreatic carcinoma among anti-diabetic medications from pre-and post-marketing evidence available from clinical trials data and pharmacovigilance databases (FAERS, VigiBase). A disproportionality analysis of pharmacovigilance data was done to statistically check whether the selected drug-event pairs were frequently reported from the database (known as a 'signal'). We performed further signal refinement analysis using OpenVigil 2.1 on the generated signals to check whether the signal sustains even after removing co-prescribed medications possessing the same risk. Also, conducted a systematic review of randomized controlled trials for evidence generation regarding the pancreatic safety of the medications. The findings from real-world data indicated that, among all anti-diabetics, incretin mimetics and sulfonylurea compounds produced signals for both pancreatitis and pancreatic carcinoma. Notable pancreatitis risk was also identified for newer anti-diabetics like SGLT-2 inhibitors. The findings from the meta-analysis of clinical trials indicated a 44% risk of DPP-4 inhibitors in causing acute pancreatitis and a 60% risk of GLP-1 agonists in elevating the lipase level, compared to placebo/active comparator. Thus, the study raises concerns over the risk of pancreatitis and pancreatic carcinoma among the users of anti-diabetic medications, especially incretin mimetics.

Comprehensive chemo-profiling of coumarins enriched extract derived from Aegle marmelos (L.) Correa fruit pulp, as an anti-diabetic and anti-inflammatory agent.

Aegle marmelos (L.) Correa is an Indian medicinal plant known for its vast therapeutic activities. In Ayurveda, the plant is known to balance "vata," "pitta," and "kapha" dosh. Recent studies suggest anti-inflammatory, anti-microbial, and anti-diabetic potential but lack in defining the dosage over the therapeutic activities. This study aims to determine the chemical profile of Aegle marmelos fruit extract; identification, enrichment, and characterization of the principal active component(s) having anti-inflammatory and anti-diabetic potential. Targeted enrichment of total coumarins, focusing on marmelosin, marmesin, aegeline, psoralen, scopoletin, and umbelliferone, was done from Aegle marmelos fruit pulp, and characterized using advanced high-throughput techniques. In vitro and in silico anti-diabetic and anti-inflammatory activities were assessed to confirm their efficacy and affinity as anti-diabetic and anti-inflammatory agents. The target compounds were also analysed for toxicity by in silico ADMET study and in vitro MTT assay on THP-1 and A549 cell lines. The coumarins enrichment process designed, was found specific for coumarins isolation as it resulted into 48.61% of total coumarins enrichment, which includes 31.2% marmelosin, 8.9% marmesin, 4% psoralen, 2% scopoletin, 1.7% umbelliferone, and 0.72% aegeline. The quantification with HPTLC and qNMR was found to be correlated with the HPLC assay results. The present study validates the potential use of Aegle marmelos as an anti-inflammatory and anti-diabetic agent. Coumarins enriched from the plant fruit have good therapeutic activity and can be used for Phytopharmaceutical ingredient development. The study is novel, in which coumarins were enriched and characterized by a simple and sophisticated methodology.

In-vitro Evaluation of Triazine Scaffold for Anticancer Drug Development: A Review.

INTRODUCTION: The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in vitro and in vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours. OBJECTIVE: The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential. CONCLUSION: The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.

How to improve regulatory practices for refurbished medical devices.

Modern health-care facilities rely on medical devices and equipment. However, keeping up with the development of new technology is unfeasible for many health facilities, especially in low-resource settings. Thus, the demand for refurbished medical devices is increasing worldwide, especially in low- and middle-income countries. Refurbished medical devices are restored devices that are rebuilt to meet safety and performance requirements comparable to their condition when new, without changing the intended use of the original device. While new medical devices are controlled by well-established and stringent safety and quality regulations, a great variation in the regulations of refurbished medical devices exists across countries. Here we discuss the different regulations and practices specific to refurbished medical devices in countries of major markets. We also explore the opportunities and challenges for expanding the refurbished medical device market. Finally, we suggest that regulatory guidelines pertaining to the import, sale, labelling and use of a refurbished medical product are needed, and authorities should implement these guidelines to ensure a high quality and safety standard of refurbished devices.

Les établissements de soins de santé modernes dépendent d'équipements et dispositifs médicaux. Pour nombre de ces établissements, il est toutefois impossible de suivre l'évolution des nouvelles technologies, surtout dans les lieux manquant de ressources. La demande en dispositifs médicaux remis à neuf est donc en hausse partout dans le monde, en particulier dans les pays à revenu faible et intermédiaire. Il s'agit de dispositifs restaurés, remaniés pour répondre aux mêmes exigences de sécurité et de performances que lorsqu'ils sont neufs, sans que l'usage prévu du dispositif d'origine ne soit modifié. Alors que les dispositifs médicaux neufs sont soumis à des normes de qualité et de sécurité strictes et bien établies, leurs équivalents restaurés font l'objet de règles nettement plus variables d'un pays à l'autre. Dans le présent document, nous évoquons les différentes réglementations et pratiques spécifiques aux dispositifs médicaux remis à neuf dans les pays qui abritent les principaux marchés. Nous nous intéressons en outre aux opportunités et aux défis liés à un développement du marché des dispositifs médicaux remis à neuf. Enfin, nous suggérons l'adoption de lignes directrices réglementaires concernant l'importation, la vente, l'étiquetage et l'utilisation de tels dispositifs; ces lignes directrices sont à faire appliquer par les autorités afin de garantir les normes les plus élevées en matière de qualité et de sécurité.

Los centros sanitarios modernos dependen de dispositivos y equipos médicos. Sin embargo, mantenerse al día en el desarrollo de las nuevas tecnologías no es viable para muchos centros sanitarios, sobre todo en los de escasos recursos. Por este motivo, la demanda de dispositivos médicos renovados está aumentando en todo el mundo, especialmente en los países de ingresos bajos y medios. Los dispositivos médicos renovados son dispositivos restaurados que se reconstruyen para que cumplan unos requisitos de seguridad y rendimiento comparables a los que tenían cuando eran nuevos, sin cambiar el uso previsto del dispositivo original. Mientras que los dispositivos médicos nuevos están sujetos a reglamentos estrictos y bien establecidos en materia de seguridad y calidad, los reglamentos de los dispositivos médicos renovados varían mucho de un país a otro. En este artículo, se analizan los diferentes reglamentos y prácticas específicos de los dispositivos médicos renovados en los países de los principales mercados. También se exploran las oportunidades y los desafíos que plantea la expansión del mercado de dispositivos médicos renovados. Por último, se propone que se establezcan directrices reglamentarias relativas a la importación, venta, etiquetado y uso de los dispositivos médicos renovados y que las autoridades las apliquen para asegurar su calidad y seguridad.

SGLT2 inhibitors associated pancreatitis: signal identification through disproportionality analysis of spontaneous reports and review of case reports.

BACKGROUND: In recent times, pancreatitis has been one of the most frequently reported adverse events for sodium-glucose cotransporter-2 (SGLT2) inhibitors. AIM: To evaluate the potential association between SGLT2 inhibitors and the risk of pancreatitis by analyzing the spontaneous reports through disproportionality analysis and reviewing case reports. METHOD: A retrospective case/non-case study was conducted using spontaneous reports from the FDA Adverse Event Reporting System (FAERS), VigiBase, and the Canadian Adverse Reaction Database (CARD). Disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and the Information Component (IC). In parallel, a review of case reports was conducted on SGLT2 inhibitors-induced pancreatitis. RESULTS: A total of 524, 510, and 40 spontaneous reports of pancreatitis suspected to be caused by SGLT2 inhibitors were identified from FAERS, VigiBase, and CARD, respectively. Through the disproportionality analysis of FAERS data, a signal was identified between the SGLT2 inhibitors and pancreatitis, with empagliflozin having highest risk [PRR = 3.9; Lower Bound (LB) ROR = 3.4; IC025 = 1.7], followed by canagliflozin [PRR = 3.6; LB ROR = 3.2; IC025 = 1.6], and dapagliflozin [PRR = 3.2; LB ROR = 2.7; IC025 = 1.4]. VigiBase and CARD data analyses reiterated the findings of FAERS. Thirteen case reports identified from a systematic literature search strengthened these findings and highlighted the importance of physical examination and laboratory parameters for the early diagnosis of pancreatitis. CONCLUSION: The current study found a potential risk of pancreatitis with the use of SGLT2 inhibitors. There is an urgent need to thoroughly investigate the same and take the necessary action to avoid or minimize the risk.

Public-private partnership (3Ps) in ensuring safe use of medicines: An Indian experience.

Adverse drug reactions (ADRs) are major concerns to the public health. To monitor ADRs and ensure patients' safety, the Pharmacovigilance Programme of India (PvPI) has been established by the Government of India in 2010. The programme is intact with the Public-Private Partnership (3Ps) in pharmacovigilance for quality services, better management of human resources and risk minimization. The present work is aimed at assessing the 3Ps engagement, performance and tangible outcomes in PvPI and also mapping of resources. The study was carried out for the period of 2011 to 2021 by assessing the various benchmarking tools such as 3Ps categorization, utilization of ADRs reporting tools, trainings, and the Individual Case Safety Reports' (ICSRs) quantity, quality and transmission for regulatory intervention (RI). Under PvPI, Central or State Government medical institutions/hospitals and public health programmes constitute public partners while private medical institutions/hospitals, pharmaceutical companies, corporate hospitals and professional bodies account for private partners. We observed that public partners extensively used ADR reporting form and toll-free helpline number while private partners used mobile based app and emails/post as preferred tools for reporting ADRs. Contribution of public sector in training programmes organized, stakeholders trained and sharing of resource materials was way higher than the private sector. The study revealed that 55.1 and 44.9% ICSRs were received from public and private partners, respectively during the study period. The quality completeness of data received from public partners was found to be 0.92/1 as compared to 0.46/1 from the private partners. The ICSRs data transmitted for RI process from the public and private partners (till 2018) was found to be 79 and 21%, respectively. In terms of sharing of resources for training and capacity building, the public sector played a major role. The 3Ps in India are enabled to establish a robust system for medicines' safety surveillance; however a more focused approach is required in mapping the resources.

Materiovigilance Programme of India: Current status and way forward.

Postmarketing vigilance system for medical devices in India is not as vigorous as of drugs. W Materiovigilance involves post marketing surveillance of adverse events caused by medical devices. As per directive of WHO, many countries including India have established their own post marketing surveillance system. In India it is known as Materiovigilance Programme of India (MvPI). This article reviews the current state of MvPI, compares it with developed countries, identifies gaps, and recommends specific measure to strengthen the existing program.

Comparative metabolic profiling, isolation of alkylated phenols and antioxidant activity of roots of Plumbago species using GC-MS and NMR based metabolomics study.

In this study, NMR and GC-MS based comparative metabolomic profiling of the roots of three different species namely, Plumbago indica, P. auriculata and P. zeylanica were investigated followed by multivariate statistical analyses and their antioxidant activity. Also, two alkylated phenols i.e., 2,6-di-tert-butyl phenol and 2,4-di-tert-butyl phenol not reported earlier from this taxon were isolated from P. indica. This metabolic study resulted in the identification of 25 and quantification of 18 metabolites. Principal component analysis showed the clear distinction among the three species. The antioxidant activity in the extracts was tested by free radical scavenging method. The three Plumbago species revealed interesting antioxidant potential, in particular, P. indica, which was rich in naphthoquinones, coumarins, alkylated phenols, sterols, triterpenes, fatty acids showed lowest IC50 value. The results highlighted the role of P. indica in the management of oxidative stress especially when they are utilized in the formation of fermented food products.

Acute intraocular toxicity caused by perfluorocarbon liquids: safety control systems of medical devices.

BACKGROUND: Acute retinal toxicity has been demonstrated to be associated with the intraoperative use of perfluorocarbon liquids (PFCLs), especially perfluorooctane (PFO). Recently, several cases of PFO-associated blindness have been reported in Spain, Holland, France, Italy, the Middle East, and South America. METHODS: As a result, a new ISO guideline (ISO 16672:2020) was drafted, discussed, approved, and released in 2019. This recent ISO16672:2020 guideline recommends performing direct cytotoxicity tests as an option along with chemical analysis to measure PFCL quality (purity and safety). RESULTS: In this review paper, it has been emphasized why an appropriate biological test, specifically direct exposure of PFCL to live cells, for measuring cytotoxicity must be performed with each PFCL batch along with chemical analysis. CONCLUSIONS: The paper intends to compile all available information to discuss possible approaches for avoiding adverse clinical cases in future.

Comparative Study of Adverse Drug Reactions Associated with Filgrastim and Pegfilgrastim Using the EudraVigilance Database.

The primary prophylaxis with filgrastim (FIL) and pegfilgrastim (PEG-F) is recommended to decrease the severity of chemotherapy-induced neutropenia (CIN). The commonly reported adverse drug reactions (ADRs) with FIL and PEG-F is bone pain. ADRs pertaining to FIL and PEG-F were extracted from the European EudraVigilance (EV) database. The Individual Case Safety Reports (ICSRs) obtained from EV database that reported FIL and PEG-F as the suspected drug were analyzed. Registered ADRs (from the groups "General disorders and administration site conditions", "Blood and lymphatic system disorders", "Musculoskeletal and connective tissue disorders" and "Investigations") for FIL and PEG-F were collected from EV database from 2007 to 5 June 2021. The reporting odds ratio (ROR) was used to calculate ICSRs with most common ADRs related to FIL and PEG-F. A total of 17,403 ICSRs described the incidence of most common ADRs of FIL and PEG-F. The commonly reported ADRs for both drugs were pyrexia, bone pain, back pain, neutropenia and febrile neutropenia. The odds ratio of ICSRs belonging to the System Organ Class (SOC) "Investigations" (ROR 1.01 (CI 0.93-1.10)) revealed no significant difference in FIL and PEG-F. However, for the SOCs (General disorders and administration site conditions" and "Musculoskeletal and connective tissue disorders" ((ROR 1.14 (CI 1.06-1.21); ROR 1.21 (CI 1.18-1.32), respectively), an increased reporting probability with PEG-F was found. The authors reported a lower reporting probability for the SOC "Blood and lymphatic system disorders" for FIL versus PEG-F (ROR 0.75 (CI 0.70-0.80)). Our results have demonstrated that the occurrence of bone pain was similar with FIL and PEG-F. For the incidence of pyrexia and back pain, PEG-F was associated with a higher reporting probability as compared to FIL. However, the incidence of neutropenia and febrile neutropenia was higher in FIL compared to PEG-F. Further evaluation of data from real life is needed.

Severe cutaneous adverse reactions in Asians: Trends observed in culprit anti-seizure medicines using VigiBase®.

PURPOSE: Diverse ethnic genetic populations display variability in the risk regarding anti-seizure medicine (ASM)-induced severe cutaneous adverse reactions (SCARs). However, clinical and epidemiological data on ASM-induced SCARs in Asians is limited. METHODS: We conducted a retrospective, post-market study until April 30, 2020 using VigiBase® for demographic characteristics, causative ASMs, complications and mortality. The study included adverse events as classified by Standardized Medical Dictionary for Regulatory Activities (MedDRA) queries of SCARs, mainly Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and SJS/TEN overlap reported for ASMs. RESULTS: A total of 694,811 adverse events were reported across the world while using ASMs. Of this, skin and subcutaneous tissue adverse events were 122,885 (17.6%). Among ASM-induced skin and subcutaneous tissue adverse events, SJS, TEN, DRESS and SJS/TEN overlap represented 11,181 (9.1%), 3,645 (3.0%), 5,106 (4.1%) and 6 (0.004%) cases, respectively. Female SJS/TEN/DRESS patients were 54.1%, and 75% of them were adults (>18Y). Nearly 64% of the ASM-induced SCARs were serious and culminated in death (3.5%), life-threatening conditions (11.5%), and hospitalization/prolonged hospitalization (43.5%) of patients on ASM therapy. Carbamazepine (31.6%), phenytoin (29.6%), lamotrigine (24.3%), valproic acid (6.4%) and phenobarbital (5.7%) are the most commonly used ASMs linked with SCARs. ASMs associated with significantly higher risk of SCARs in Asians were carbamazepine [n = 3265, ROR 3.55 (95% CI 3.38-3.72, P < 0.0001)], lamotrigine [n = 1253, ROR 3.90 (95% CI 3.63-4.18, P < 0.0001)], gabapentin [n = 85, ROR 3.58 (95% CI 2.79-4.60, P < 0.0001)], pregabalin [n = 68, ROR 3.16 (95% CI 2.40-4.16, P < 0.0001)], clonazepam [n = 53, ROR 3.19 (95% CI 2.31-4.41, P < 0.0001)], lorazepam [n = 31, ROR 3.07 (95% CI 2.06-4.59, P < 0.0001)] and acetazolamide [n = 28, ROR 3.90 (95% CI 2.45-6.21, P < 0.0001)]. CONCLUSION: Based on our study, carbamazepine, lamotrigine, gabapentin, pregabalin, clonazepam, lorazepam, and acetazolamide are the most common causative ASMs for SCARs in the Asian population.

Analysis of severity and preventability in patients of-Toxic epidermal necrolysis-A case series.

SJS-TEN is life-threatening autoimmune disorder triggered due to drugs such as analgesics, antibiotics, anticonvulsants, and antipsychotics. This report provides awareness to the Clinicians regarding prescription of drugs which cause SJS-TEN. Among young females of 20-40 years, screening for previous history, issuing drug alert cards, and preventing OTC prescriptions decreases mortality.

Ajmalicine and Reserpine: Indole Alkaloids as Multi-Target Directed Ligands Towards Factors Implicated in Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disorder characterized by exponential loss of memory and cognitive deficit involving several disease modifying targets (amyloid beta, beta-secretase, monoaminoxidase-B, and cholinesterase). The present study explores multi-target directed ligand approach using secondary metabolite reserpine (RES) and ajmalicine (AJM) obtained from Rauwolfia serpentina roots. Novel LCMS and HPLC methods were developed for identification and quantification of reserpine and ajmalicine. In vitro enzyme inhibition assays were performed to evaluate anti-cholinesterase, ß-site amyloid cleaving enzyme (BACE-1) inhibition and monoamine oxidase-B (MAO-B) inhibition, further analyzed with in silico analysis. Anti-amyloidogenic potential was studied using anti-aggregation studies along with TEM and circular dichroism (CD) analysis. In vitro neuroprotective potential against Aß toxicity and anti-oxidative stress was demonstrated using PC12 cell cultures. Reserpine is a more potent dual cholinesterase inhibitor than ajmalicine (IC50 values of 1.7 µM (AChE) and 2.8 µM (BuChE)). The anti-aggregation activity of reserpine (68%) was more than ajmalicine (56%). Both compounds demonstrated neuroprotective activity against Aß42 (92%) and H2O2 (93%) induced toxicity in PC12 cells against controls. Phytocompounds also inhibited MAO-B and BACE-1 enzymes in concentration dependent manner. Molecular docking studies indicated the strong binding of compounds to the catalytic site of targets. This novel study demonstrated that reserpine and ajmalicine as a multi-target directed ligand that have disease modifying potential for amelioration of AD.

Towards a comprehensive safety understanding of granulocyte-colony stimulating factor biosimilars in treating chemotherapy associated febrile neutropenia: Trends from decades of data.

Filgrastim, a biopharmaceutical listed on WHO model list of essential medicines, was approved in USA in 1991 for patients with non-myeloid malignancies associated with severe neutropenia and fever. Several filgrastim biosimilars have now been approved in USA, Europe and elsewhere since 2008, based on the reference product which has lost patent exclusivity; however their immunogenicity and safety is controversial. We conducted a retrospective, post market study between 1991 and May 2018 using VigiBase®. The study included all adverse events with case reports ≥150. Overall, 11,183 adverse drugs reaction reports were identified during observation period; of which 5764; 51.5% reports concerned to Neupogen®, the originator, and rest consists of Leucostim® (N = 680), Zarzio® (N = 622), Grasin® (N = 545), Nivestim® (N = 359) and Tevagrastim® (N = 152) biosimilars. When compared with the originator, Grasin® was associated with higher reporting of pyrexia (11.5% vs 7.9%, ROR 1.52, IC025 1.12), myalgia (37% vs 2.2%, ROR 25.94, IC025 2.11) and back pain (11.3% vs 4%, ROR 3.09, IC025 2.32). Zarzio® was associated with increased reporting of arthralgia (4.5% vs 2.9%, ROR 1.59, IC025 1.25) and neutropenia (11.4% vs 4%, ROR 2.59, IC025 3.07). Bone pain was reported more often with Nivestim® (14.4% vs 8.3%, ROR 1.87, IC025 5.30). Drug ineffectiveness was reported in cases with Zarzio® (35.9%), Nivestim® (19.4%) and Tevagrastim® (42.2%). Authors observed significant differences among originator and biosimilars in particular to efficacy, adverse events reported and time to onset of occurrences. Large epidemiologic studies are needed to further confirm these finding and provide additional insights.

Implementation of adverse event reporting for medical devices, India.

PROBLEM: Rapid growth in the use of medical devices has drawn attention to gaps in the systematic monitoring of medical device-associated adverse events in India. APPROACH: Implementation of national regulations on medical devices started in January 2018. Supported by a nationwide network of monitoring centres, the Indian Pharmacopoeia Commission coordinates adverse event reports from manufacturers, legal representatives and patients or users. The commission follows-up and reviews reports with subject expert groups and sends recommendations on necessary action to the national regulatory authority. LOCAL SETTING: Before 2015, no systematic structure was in place to collate adverse events associated with medical devices. Several reports of deaths and hospitalization due to faulty hip implants, cardiac stents and poor-quality devices prompted the health ministry to launch the materiovigilance programme. RELEVANT CHANGES: From July 2015 to October 2019, the commission received 1931 adverse event reports, mostly from marketing authorization holders; 1277 were serious events. Reporting increased markedly after 2017. Cardiac stents were the most reported device (926 events; 47.95%). To encourage a culture of reporting, the commission has raised awareness about the programme among stakeholders, developed user-friendly reporting tools and guidelines, and conducted training for hospital personnel on medical device adverse event reporting. LESSONS LEARNT: Regular training to stakeholders develops a sense of responsibility towards reporting medical device adverse events and ensures quality data reporting. Reporters must be assured that reporting adverse events does not have any legal implications for them and given acknowledgement of their role in high-quality device associated adverse event reporting.

"ADR PvPI" Android mobile app: Report adverse drug reaction at any time anywhere in India.

BACKGROUND: To improve the public health and promote instant adverse drug reaction (ADR) reporting, a need to develop an ADR Pharmacovigilance Programme of India (PvPI) mobile app was identified by the National Coordination CentrePvPI (NCCPvPI) to serve the Pan India ADR reporting. The objective of this study was to develop an indigenous Googlebased Android mobile application known as "ADR PvPI" and to analyze the ADRrelated data reported through this mobile application on pilot basis. MATERIALS AND METHODS: The ADR PvPI mobile application was indigenously developed by NCCPvPI officials within 6 months. The study of spontaneous ADR reporting was carried out between September 2017 and September 2018. This article provides an overview of the salient features of ADR PvPI mobile application, guides on how to fillin ADRs, reporting trends of ADR, types of ADR as per System Organ Class and pharmacological classes of drugs. RESULTS: Till date, >5500 users have downloaded the app with an average rating of 4.26. In that tenure, 262 reports have been received through ADR PvPI mobile app. During the year 2017, 3.55% of reports were received through ADR PvPI mobile app and the percentage of reports received by 2018 was 96.45%. CONCLUSION: The frequency of ADR reporting has significantly increased over the past 1 year and should be promoted further through awareness and training programs.